Antibodies targeting Glycoprotein VI

Abstract

The present disclosure provides antibodies or antibody fragments specific for GPVI. In particular, it relates to antibodies or antibody fragments that have combined beneficial properties and are therefore useful for the treatment or prophylaxis of GPVI related disorders or conditions, such as for example thrombotic or vascular disorders.

The invention claimed is: 
     
       1. An antibody or antibody fragment specific for GPVI, wherein said antibody or antibody fragment comprises
 a) the HCDR1 region of SEQ ID NO: 11, the HCDR2 region of SEQ ID NO: 12, the HCDR3 region of SEQ ID NO: 13, the LCDR1 region of SEQ ID NO: 14, the LCDR2 region of SEQ ID NO: 15 and the LCDR3 region of SEQ ID NO: 16, or 
 b) the HCDR1 region of SEQ ID NO: 22, the HCDR2 region of SEQ ID NO: 23, the HCDR3 region of SEQ ID NO: 24, the LCDR1 region of SEQ ID NO: 25, the LCDR2 region of SEQ ID NO: 26 and the LCDR3 region of SEQ ID NO: 27, or 
 c) the HCDR1 region of SEQ ID NO: 33, the HCDR2 region of SEQ ID NO: 34, the HCDR3 region of SEQ ID NO: 35, the LCDR1 region of SEQ ID NO: 36, the LCDR2 region of SEQ ID NO: 37 and the LCDR3 region of SEQ ID NO: 38, or 
 d) the HCDR1 region of SEQ ID NO: 44, the HCDR2 region of SEQ ID NO: 45, the HCDR3 region of SEQ ID NO: 46, the LCDR1 region of SEQ ID NO: 47, the LCDR2 region of SEQ ID NO: 48 and the LCDR3 region of SEQ ID NO: 49. 
 
     
     
       2. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment comprises
 a) the VH of SEQ ID NO: 17 and the VL of SEQ ID NO: 18, or 
 b) the VH of SEQ ID NO: 28 and the VL of SEQ ID NO: 29, or 
 c) the VH of SEQ ID NO: 39 and the VL of SEQ ID NO: 40, or 
 d) the VH of SEQ ID NO: 50 and the VL of SEQ ID NO: 51. 
 
     
     
       3. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment comprises
 a) the HC of SEQ ID NO: 20 and the LC of SEQ ID NO: 19, or 
 b) the HC of SEQ ID NO: 21 and the LC of SEQ ID NO: 19, or 
 c) the HC of SEQ ID NO: 31 and the LC of SEQ ID NO: 30, or 
 d) the HC of SEQ ID NO: 32 and the LC of SEQ ID NO: 30, or 
 e) the HC of SEQ ID NO: 42 and the LC of SEQ ID NO: 41, or 
 f) the HC of SEQ ID NO: 43 and the LC of SEQ ID NO: 41, or 
 g) the HC of SEQ ID NO: 53 and the LC of SEQ ID NO: 52, or 
 h) the HC of SEQ ID NO: 53 and the LC of SEQ ID NO: 54. 
 
     
     
       4. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment is a human, humanized, chimeric or synthetic antibody or antibody fragment. 
     
     
       5. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment is an isolated antibody or antibody fragment. 
     
     
       6. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment is a recombinant antibody or antibody fragment. 
     
     
       7. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment is a monoclonal antibody or antibody fragment. 
     
     
       8. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment is a monovalent antibody or antibody fragment. 
     
     
       9. An antibody fragment according to  claim 8 , wherein said monovalent antibody fragment is a Fab. 
     
     
       10. An antibody or antibody fragment according to  claim 9 , wherein said Fib comprises a modified heavy chain constant region, wherein the modified heavy chain constant region comprises the amino acid sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKEVERRQGGIGHKC (SEQ ID NO: 113 and wherein the modified heavy chain constant region inhibits recognition of said Fab by anti-Fab antibodies present in a subject's serum. 
     
     
       11. An antibody or antibody fragment according to  claim 10 , wherein the modified heavy chain constant region consists of the amino acid sequence 
       
         
           
                 
               
                   (SEQ ID NO: 113) 
                 
                   ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV 
                 
                     
                 
                   HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKEVER 
                 
                     
                 
                   RQGGIGHKC. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
       12. An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment is specific for human GPVI, cynomolgus monkey GPVI, mouse GPVI and rat GPVI. 
     
     
       13. An antibody or antibody fragment according to  claim 1  for use in medicine. 
     
     
       14. An antibody or antibody fragment according to  claim 1  for use in the treatment of a subject in need thereof. 
     
     
       15. A nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding the antibody or antibody fragment according to  claim 1 . 
     
     
       16. A vector composition comprising a vector or a plurality of vectors comprising the nucleic acid sequence or plurality of nucleic acid sequences of  claim 15 . 
     
     
       17. A host cell comprising the vector composition of  claim 16 . 
     
     
       18. A pharmaceutical composition comprising an isolated antibody or antibody fragment according to  claim 1  and a pharmaceutically acceptable carrier or excipient.